Comparison of HPV and cytology triage algorithms for women with borderline or mild dyskaryosis in population‐based cervical screening (VUSA‐screen study)

Abstract

We studied the effectiveness of high-risk human papillomavirus (hrHPV) triage for immediate colposcopy in women with borderline or mild dyskaryosis (BMD). In the Utrecht province of the Netherlands, women aged 30-60 years who participated in the regular cervical screening programme were offered hrHPV testing and cytology (intervention group) or cytology only (control group). In the intervention group (n 5 337), women with BMD were immediately referred for colposcopy only if the sample was hrHPV positive. Women with a hrHPV negative test were advised to repeat cytology at 6 and 18 months and were referred for colposcopy if and when the repeat test result was positive (BMD or worse). In the control group (n 5 329), referral of women with BMD was delayed until cytology was repeatedly positive at 6 or 18 months. The CIN3 detection rates were 10.7% (36/337) in the intervention group and 6.4% (21/329) in the control group (p 5 0.047). Moreover, hrHPV triaging resulted in shorter time to diagnosis (154 vs. 381 days). Although the number of colposcopy referrals was 51.5% higher in the intervention group than in the control group, the medical costs per detected CIN3 were slightly lower ([euro] 4781 vs.[euro] 6235). If, in addition, hrHPV negative women had been referred back to routine screening at baseline, the CIN3 rate would have been 10.1% (34/337) and colposcopy rate would only have been 30.4% higher than in the control group. This study shows that hrHPV triaging of women with BMD is at least as effective for detecting CIN3 as repeat cytology, also when hrHPV negative women are referred back to routine screening.In many European population-based screening programmes, women with borderline or mild dyskaryosis (BMD) are recalled for repeat cytology before being referred for colposcopy only if the cytological abnormality persists. This policy is used because only 5-15% of these women have or will develop high-grade cervical lesions.1-3 A disadvantage of repeat testing is that women may become lost during follow-up. 4 Repeat cytology also induces a considerable amount of side effects in terms of psychological distress. 5,6 Several groups have studied the possible value of hrHPV testing and cytology for the detection of cervical lesions. 7,8 Most studies show that hrHPV testing is a sensitive instrument to triage women with BMD, but the optimal triaging strategy remains controversial. 9,10 In the Netherlands, women with BMD are followed with cytology testing at 6 and 18 months. Since 2006, screening laboratories may choose to include a hrHPV test in the repeat cytology at 6 months.11 This leads to a reduction in the number of repeat smears as it is considered safe to refer women with normal cytology and a negative hrHPV test back to the routine screening. A more substantial reduction in the number of repeat smears is expected when women with BMD are tested for hrHPV at baseline. However, population-based prospective evidence, in terms of the end-points CIN3 or cancer (CIN3þ), colposcopy referrals and medical costs needed...

Genome-wide methylome analysis using MethylCap-seq uncovers 4 hypermethylated markers with high sensitivity for both adeno- and squamous-cell cervical carcinoma

“…within each diagnosis group – from 27 women diagnosed without CIN (median age: 36, IQR 30-48), 38 with CIN1 (median age: 40, IQR 31 to 45), 45 CIN2 (median age: 35, IQR 31-40), 61 CIN3 (median age: 35, IQR 32-40), 14 adenocarcinoma in situ (AdCIS) (median age: 36, IQR 32-44) and 44 with (micro-invasive) carcinoma (median age: 40, IQR 36-50). Of the AdCIS scrapings 3 were collected at the Meander Medical Centre (Amersfoort, the Netherlands) and 6 at the VU University Medical Centre (Amsterdam, the Netherlands) [75, 76]. The (mi)Ca cases comprised 12 ADC (median age: 40, IQR 36 to 49), 29 SCC (median age: 40, IQR 36 to 50) and 3 adenosquamous carcinomas (see Supplementary Table S5).…”

Clinical Validation of the cobas 4800 HPV Test for Cervical Screening Purposes

“…The clinical performance of the cobas 4800 HPV test was assessed relative to HC2, which detects 13 hrHPV types (i.e., HPV16, -18, -31, -33, -35, -39, -45, -51, -52, -56, -58, -59, and -68), in a cohort of screening participants originally screened by cytology and HC2 cotesting (intervention group of the VUSA-Screen trial) (5,6). A detailed description of the VUSA-Screen trial, including the referral policy and follow-up procedure, has been published previously (6).…”

“…A detailed description of the VUSA-Screen trial, including the referral policy and follow-up procedure, has been published previously (6). Informed consent was obtained from all study participants, and this study followed the local ethical guidelines of the medical center.…”

Five-Year Cervical (Pre)Cancer Risk of Women Screened by HPV and Cytology Testing

“…1. Inclusion and exclusion criteria have been described previously (3). Briefly, 25,871 women participating in the regular cervical screening program were offered an HPV test in addition to cytology.…”

“…Thus, proper triage algorithms using additional tests for HPV-positive women are necessary. Previously, we have determined the risk within 36 months for CIN2þ and CIN3 or worse (CIN3þ) in the VUSA-Screen cohort (3,4). In this context, we have also evaluated several triage algorithms (5).…”